Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family
Resumen: The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease.
Idioma: Inglés
DOI: 10.1093/brain/awx295
Año: 2018
Publicado en: Brain 141, 1 (2018), 55-62
ISSN: 0006-8950

Factor impacto JCR: 11.814 (2018)
Categ. JCR: NEUROSCIENCES rank: 11 / 266 = 0.041 (2018) - Q1 - T1
Categ. JCR: CLINICAL NEUROLOGY rank: 6 / 199 = 0.03 (2018) - Q1 - T1

Factor impacto SCIMAGO: 5.978 - Neurology (clinical) (Q1) - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/FIS/PI14-00005
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI14-00070
Tipo y forma: Article (Published version)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)

Creative Commons You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.


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 Record created 2018-02-16, last modified 2020-01-17


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